Highlights of recently published NIDA-supported studies

Incentives Reduce Stimulant Abuse During Methadone Maintenance

Methadone maintenance patients who earned chances to win prizes by providing stimulant-negative urine samples were twice as likely as those who received usual care to attain abstinence from these drugs in a study conducted at six outpatient programs. Dr. Maxine Stitzer and colleagues in the NIDA Clinical Trials Network found that adding an abstinence-based incentive to usual care—daily methadone and individual and group counseling at least once a month—tripled the likelihood of continuous stimulant abstinence for 4 or more weeks during the 12-week study. Prizes for the incentive program cost about $120 for each of the 388 participants, on average, or $1.42 a day. Prize-based incentives have proven successful in helping stimulant abusers attain abstinence during community-based treatment (see "Low-Cost Incentives Improve Outcomes in Stimulant Abuse Treatment"), and the new findings demonstrate the intervention's efficacy for a diverse population of opioid-addicted patients receiving usual care in typical treatment settings.
Archives of General Psychiatry 63(2):201-208, 2006. [Abstract]

Naltrexone-Nicotine Patch Combination Shows Promise

Supplementing nicotine replacement therapy with naltrexone yielded improvements in outcomes in a double-blind 6-week trial. Among the 295 enrollees who completed the trial, quit rates were 72 percent with 100 mg of naltrexone, 51 percent with 25 mg, 48 percent with 50 mg, and 48 percent with a naltrexone placebo. Patients who took the 100 mg dose reported the greatest reductions in nicotine cravings and withdrawal symptoms. The investigators observed that patients receiving the 25 mg and 50 mg doses gained the least weight, and suggested that combination therapy with low-dose naltrexone and the patch be considered for smokers concerned about weight gain. The researchers cautioned that naltrexone augmentation for smoking cessation requires further study, as abstinence differences evened out by a 3-month followup, and did not recur at 6- and 12-month followups.
Archives of Internal Medicine 166(6):667-674, 2006. [Abstract]

Scientists Pinpoint Brain's Sweet Tooth

Drs. Susana Peciña and Kent Berridge of the University of Michigan have traced rats' liking for sweets to a 1-cubic millimeter site in the medial shell of the nucleus accumbens. Using fine-grained brain mapping, the researchers correlated mu-opioid activation of this area [by D-Ala²-N-Me-Phe⁴-Glycol⁵-enkephalin (DAMGO)] with the facial reactions rats exhibit upon receiving infusions of sweet tastes into the mouth. Enhancing mu-opioid activity in this hedonic "hot spot" produced two to four times the number of positive reactions (e.g., licking) to sucrose relative to other regions of the medial shell. Stimulating the hot spot with DAMGO also reduced the rats' negative reactions to a bitter taste by 25 percent. The findings suggest that opioid circuits in the medial shell involved in liking (e.g., positive facial expressions in reaction to a taste) and wanting (e.g., pressing a lever for a substance) are related but not identical, as activating mu-opioid circuits in widely distributed areas of the medial shell increased food intake.
The Journal of Neuroscience 25(50):11777-11786, 2005. [Full Text]

Antipsychotic Drug Prevents Morphine Tolerance in Mice

Dr. Zaijie Jim Wang and colleagues at the University of Illinois suppressed morphine tolerance and dependence in mice by blocking calcium/calmodulin-dependent protein kinase II (CaMKII), which may contribute to chronic pain in the central nervous system. In a followup study, the investigators found elevated levels of CaMKII activity in the brain and spinal cord (an 81 percent and 222 percent increase, respectively) of mice displaying morphine tolerance compared with mice that did not. Trifluoperazine, an antipsychotic drug and a CaMKII inhibitor newly identified by these researchers, prevented both the increase in CaMKII activity and the development of opioid tolerance and disrupted established opioid tolerance in the animals. The findings suggest that CaMKII-suppressing drugs may reduce morphine tolerance and ultimately be of value in treating pain and fighting opioid addiction.
Neuroscience Letters 397(1-2):1-4, 2006; [Abstract]
Journal of Pharmacology and Experimental Therapeutics 317(2): 901-909, 2006. [Abstract]

Volume 21, Number 3 (April 2007)